The Challenge Area addressed by this project is Area 9: Health Disparities Research. The specific topic for this application is "Prevention Strategies that Target Disproportionately Affected Lupus and Scleroderma Patient Populations". Systemic lupus erythematosus is a prototypic systemic autoimmune disease for which no new FDA treatment has been approved in over 50 years. Identification of "high risk" groups for SLE development would allow intervention with preventive therapies. Systemic lupus has a known genetic predisposition and family members are carry an increased risk of developing clinical disease. Over the past 15 years, our consortium of investigators has assembled a collection of nearly 6,000 unaffected blood relatives of SLE patients who had serum samples collected and stored on average 7.6 years ago. These individuals were clinically well at that time, but many have potentially transitioned to clinical lupus in the interim. Re-contacting these individuals (who have provided consent for re-contact for future studies) will provide us with a unique opportunity to rapidly assemble a group of SLE patients with specimens before and at/after clinical disease onset. In addition, cohorts of individuals with some increased genetic risk, and likely autoantibodies, who do not transition to clinical disease will be compiled. Select serological biomarkers, including select autoantibody profiles and serum alpha interferon activity, will be tested for association with transition to clinical lupus. Additional lupus- associated environmental factors, such as markers of vitamin D deficiency and abnormal humoral immune responses to common pathogens, will be tested as predictors of SLE disease onset. Evaluation of genetic risk polymorphisms with increased risk of SLE can be further studied. Finally, a large collection of clinical, demographic, and therapeutic information, in combination with biospecimens from historical collections and follow-up studies, will be available for future investigation. This project will help to identify "high risk" individuals for SLE development, defining outstanding populations for potential preventative therapies directed toward these or future biomarkers. Autoimmune diseases are estimated to afflict as many as 50,000,000 Americans. PUBLIC HEALTH RELEVANCE: This application tests genetic and serologic biomarkers of autoimmunity, cytokine activity, and abnormal environmental responses as predictors of autoimmune disease onset. ARRA funds would allow rapid generation of a SLE transition cohort by follow-up of historical, at-risk individuals to establish disease predictors to aid in prevention strategies. Biospecimens and associated clinical data will be biobanked to test future alternate hypotheses.